Abstract

Background: The objective of this study was to evaluate if anticoagulation therapy reduces recurrent stroke in embolic stroke of undetermined source (ESUS) patients with left atrial enlargement (LAE) or abnormal markers of coagulation and hemostatic activity (MOCHA) compared to antiplatelet therapy.Methods: ESUS patients from January 1, 2017, to June 30, 2019, underwent outpatient cardiac monitoring and the MOCHA profile (serum d-dimer, prothrombin fragment 1.2, thrombin–antithrombin complex, and fibrin monomer). Anticoagulation was offered to patients with abnormal MOCHA (≥2 elevated markers) or left atrial volume index 40 mL/m2. Patients were evaluated for recurrent stroke or major hemorrhage at routine clinical follow-up. We compared this patient cohort (cohort 2) to a historical cohort (cohort 1) who underwent the same protocol but remained on antiplatelet therapy.Results: Baseline characteristics in cohort 2 (n = 196; mean age = 63 ± 16 years, 59% female, 49% non-White) were similar to cohort 1 (n = 42) except that cohort 2 had less diabetes (43 vs. 24%, p = 0.01) and more tobacco use (26 vs. 43%, p = 0.04). Overall, 45 patients (23%) in cohort 2 initiated anticoagulation based on abnormal MOCHA or LAE. During mean follow-up of 13 ± 10 months, cohort 2 had significantly lower recurrent stroke rates than cohort 1 (14 vs. 3%, p = 0.009) with no major hemorrhages.Conclusions: Anticoagulation therapy in a subgroup of ESUS patients with abnormal MOCHA or severe LAE may be associated with a reduced rate of recurrent stroke compared to antiplatelet therapy. A prospective, randomized study is warranted to validate these results.

Highlights

  • One-third of ischemic strokes are categorized as cryptogenic strokes, and estimates suggest that approximately one-sixth of ischemic strokes meet diagnostic criteria for embolic stroke of undetermined source (ESUS) [1, 2]

  • Subgroup analysis of patients enrolled in the Warfarin-Aspirin Recurrent Stroke Study trial with elevated N-terminal pro–brain natriuretic peptide showed a beneficial effect of anticoagulation in prevention of recurrent stroke [5]

  • The objective of this study was to evaluate if anticoagulation therapy reduces recurrent stroke in ESUS patients who have left atrial enlargement (LAE) on echocardiography or abnormal markers of coagulation and hemostatic activity (MOCHA) profile

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Summary

Introduction

One-third of ischemic strokes are categorized as cryptogenic strokes, and estimates suggest that approximately one-sixth of ischemic strokes meet diagnostic criteria for embolic stroke of undetermined source (ESUS) [1, 2].Anticoagulation therapy for ESUS patients has been postulated to prevent recurrent ischemic strokes; empiric treatment with anticoagulation for patients with ESUS has not been deemed beneficial in large randomized controlled trials of unselected cohorts [1, 3]. Secondary analysis of NAVIGATE ESUS [4] demonstrated a beneficial effect of anticoagulation in subset of patients with moderate to severe left atrial enlargement (LAE) [4]. Subgroup analysis of patients enrolled in the Warfarin-Aspirin Recurrent Stroke Study trial with elevated N-terminal pro–brain natriuretic peptide showed a beneficial effect of anticoagulation in prevention of recurrent stroke [5]. The markers of coagulation and hemostatic activity (MOCHA) profile has been shown to identify patients with occult atrial fibrillation, venous thromboembolism, or undiagnosed underlying malignancy [6, 7]. The objective of this study was to evaluate if anticoagulation therapy reduces recurrent stroke in embolic stroke of undetermined source (ESUS) patients with left atrial enlargement (LAE) or abnormal markers of coagulation and hemostatic activity (MOCHA) compared to antiplatelet therapy

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